1. Field of the Invention
The present invention relates generally to synthetic compounds which are useful as artificial sweeteners to be used in connection with beverages and foodstuffs designed for human consumption. More particularly, the present invention relates to the discovery of a new bridged carboxylic ortho ester which possesses an intense sweet taste and is suitable for use as an artificial sweetener.
2. Description of Related Art
Aspartame (L-aspartyl-L-phenylalanine methyl ester) is a well-known artificial sweetener which was accidentally discovered by James M. Schlatter in the 1960's (Mazur, R. H. Food Sci. and Technol., 1984, 12, 3). Since its discovery, aspartame and a number of derivatives of this remarkable and potent sweetener have been subjected to many investigations. For example, Mazur et al. found that substitution of the aspartyl moiety leads to bitter or tasteless analogues (Mazur, R. H. Schlatter, J. M.; Goldkamp, A. H. J. Am. Chem. Soc., 1969, 91, 2684). Other investigations involved replacing the phenylalanine methyl ester group with a wide variety of different amino acids providing either D-configurations with a small side chain and a large ester group or an L-configuration with a large side chain and a small ester group (See Grenby, T. H. (ed.), Progress in Sweeteners, Elssevier Applied Science, London, N.Y.).
In other studies, L-aspartyl-alanine 2,2,5,5,-tetramethylcyclopentyl amides and analogous retro-inverso derivatives have been investigated. For these compounds, it was observed that the L,L amide had a bitter taste while the L,D amide and the retro-inverso analogues had a sweet taste (Fuller, W. D.; Goodman, M.; Verlander, M. S. J. Am. Chem. Soc., 1985, 107, 821).
A number of conformational studies have been undertaken to establish and explain the relationship between the structure and sweet taste of these compounds. For example, conformational studies using computer simulation, NMR and X-ray diffraction have been used to propose structural models for sweet tasting compounds (See Goodman, M.; Coddington, J.,; Mierke, D. F.; Fuller, W. D. J. Am. Chem. Soc. 1987, 109, 4712 and Goodman, M.; Miercke, D. F.; Fuller, W. D. in: Peptide Chemistry: Proceedings of the Japan Symposium on Peptide Chemistry, T. Shiba, S. Sakakibara (eds.), Protein Research Foundation, Japan 1988, pp. 699-704).
Even though aspartame and various dipeptide analogues have been studied extensively, it is still difficult to predict with any certainty the relationship between specific structures and their taste. For example, it has been observed repeatedly that small structural changes in various aspartame analogues can have dramatic effects on the taste of the compound. As a result, the discovery of new synthetic sweeteners is still unpredictable.